What question did this study set out to answer?

The aim is to explore the effects of high-fat diet duration on lipid metabolism in hyperlipidemia mouse models.

February 8, 2026International Journal of Molecular Sciences0 citationsOpen Access

Lipophagy Dynamics in Hyperlipidemia Model ICR Mice Across Different High-Fat-Diet Feeding Durations

Key Points

The aim is to explore the effects of high-fat diet duration on lipid metabolism in hyperlipidemia mouse models.
Induced hyperlipidemia in ICR mice using high-fat diet for varying durations (3-15 weeks).
Measured body weights and organ indices alongside serum and liver lipid levels.
Assessed pathological changes using Oil Red O and HE staining methods.
Evaluated related pathway markers using immunofluorescence, qPCR, and Western blotting.
At 9 weeks, protein expression ratios of P-AMPK/AMPK and P-mTOR/mTOR were significantly reduced.
Elevated levels of LC3Ⅱ/LC3Ⅰ and P62 proteins indicated lipid metabolism dysregulation.
Identified potential optimal time point for modeling hyperlipidemia in ICR mice.

Abstract

Hyperlipidemia (HLP) is a metabolic dysfunction marked by dysregulated lipid metabolism, which jeopardizes cardiovascular health. The function of autophagy modulated by the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in HLP pathogenesis has not been fully elucidated. Thus, this study centered on the impacts of different feeding durations on HLP models. ICR mice were given a high-fat diet (HFD) to induce the model, with durations set at 3, 6, 9, 12, and 15 weeks. Body weight, liver and adipose organ indices, serum and hepatic lipid levels, and pathological changes (assessed by Oil Red O and HE staining) were measured. Related pathway markers were detected via immunofluorescence, quantitative real-time PCR (qPCR), and Western blotting. At week 9, the relative protein expression ratios of P-AMPK/AMPK, P-mTOR/mTOR, and P-ULK1/ULK1 were markedly reduced, while the expression levels of LC3Ⅱ/LC3Ⅰ and P62 proteins were notably elevated, exhibiting transient dysregulation characteristics and suggesting a potential optimal modeling time point. It clarifies the temporal pattern, core molecular mechanism, and critical turning point of abdominal adipose metabolic disorder induced by a high-fat diet (HFD) in ICR mice. This study offers a credible basis for the optimal duration of HLP modeling and in vivo animal experimental design.

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